Despite Delay in HLH Diagnosis, Patient in Complete Remission After Chemotherapy for Lymphoma, Case Study Reports

Despite Delay in HLH Diagnosis, Patient in Complete Remission After Chemotherapy for Lymphoma, Case Study Reports

Despite a five-month delay in his hemophagocytic lymphohistiocytosis (HLH) diagnosis, a 63-year-old man with lymphoma achieved complete remission after six cycles of a brentuximab-based chemotherapy, a case study reports.

The study, “Hodgkin’s lymphoma with HLH and complete remission with brentuximab-based therapy,” was published in the journal BMJ Case Reports.

HLH is a disease characterized by excessive inflammation and tissue destruction due to an impairment of the immune system. The two different types of the disease are primary HLH, which is inherited, and secondary HLH, which is often triggered by cancers, rheumatological disorders, or infections — Epstein-Barr virus (EBV) is the most well-known infection that can trigger HLH.

The criteria for identifying HLH are not specific and commonly used for other disorders, making diagnosis challenging. However, untreated HLH can be fatal so a prompt diagnosis is vital.

In the study, researchers at the Loyola University Medical Center report the case of a 63-year-old man who achieved complete remission after undergoing brentuximab-based chemotherapy for Hodgkin’s lymphoma, even though it took five months to diagnose him with HLH.

When admitted to hospital in August 2018, the man had progressive weakness, fatigue, and a 22 kg (48.5 lb) weight loss. Upon clinical examination, which showed an enlargement of the mediastinal lymph nodes (located in the part of the chest that lies between the sternum and spinal column), he was diagnosed with sarcoidosis.

Sarcoidosis is a disease marked by an over-reactive immune system that leads to the formation of small clumps of inflammatory cells called granulomas in different tissues and organs.

The patient began treatment with prednisone, an FDA-approved corticosteroid, which led to a temporary improvement of his cough and fatigue. As prednisone was tapered down, he was given weekly oral methotrexate, a disease-modifying anti-rheumatic drug used to reduce the activity of the immune system.

However, the patient’s fatigue, weakness, and weight loss continued to progress, which prompted him to go to the emergency room.

On examination, he showed a deficiency in several blood cells, was anemic — his hemoglobin level was 57 g/L (normal values range from 130–175 g/L) — and had low platelet counts (82×109/L, while reference values range between 140 to 400×109/L). He did not have a fever at the time.

The patient then underwent a CT scan to the chest, abdomen, and pelvis. Pulmonologists were skeptical of his sarcoidosis diagnosis, as he did not exhibit key features, such as hilar lymphadenopathy (enlarged lymph nodes in the lung root). Meanwhile, the man developed a high fever and had elevated ferritin (an indicator of too much iron).

Altogether, his symptoms led clinicians to suspect HLH.

“These clinical manifestations of persistently high fever, cytopenia [lower levels of blood cells], organomegaly [organ enlargement], and elevated ferritin, the diagnosis of HLH was considered,” they wrote.

The patient was positive for five out of the eight criteria of the HLH-2004 diagnostic criteria. These included fever, splenomegaly (enlargement of the spleen), cytopenia (lower levels of blood cells), hypertriglyceridemia (high levels of fat called triglycerides), and elevated ferritin.

His calculated H-score, which measures the likelihood of having HLH, was above 260, “which predicts a high probability of HLH,” the researchers wrote.

A biopsy of the bone marrow and lymph nodes showed evidence of hemophagocytosis (engulfment of blood cells), meeting another criteria for HLH diagnosis. The results also showed evidence of classic Hodgkin’s lymphoma — a cancer in the lymphatic system.

Furthermore, the patient was found to be positive for EBV infection.

“He was transferred to the inpatient hematology service with a diagnosis of HLH secondary to classic Hodgkin’s lymphoma in the setting of EBV viraemia,” the researchers wrote.

Treatment was started for HLH (one dose of etoposide and Decadron), followed by lymphoma-directed therapy — namely with AVD (doxorubicin, vinblastine and dacarbazine). The patient was discharged 14 days after admission, and continued AVD treatment with the addition of brentuximab. Nine months later, he had completed six cycles of AVD plus brentuximab.

The patient is now in complete remission for his disease, based on positron-emission tomography imaging analysis and bone marrow biopsy.

“Malignancy-associated HLH has a poor prognosis mainly due to a delay in diagnosis and initiation of appropriate therapy,” the researchers wrote.

“Fortunately for our patient, despite a delay of 5 months in diagnosis and development of HLH, he still achieved complete remission after appropriate treatment of his underlying Hodgkin’s lymphoma,” they said.

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